Embryonic stem (ES) cells are derived from totipotent cells in an embryo. Murine ES cells have been shown to be pluripotent cells capable in vitro of terminal differentiation into cells of the mesoderm, ectoderm and endoderm lineages (Robertson, 1987; Dushnik-Levinson and Benvenisty, 1995). The pluripotency of murine embryonic stem cells has been established on the basis of three criteria:                (1) When undifferentiated murine ES cells are injected into the cavity of a blastocyst and the blastocysts are subsequently implanted into pseudo-pregnant mice, chimeric mice develop. The injected ES cells contribute to all cell types, including the germ layer. Thus, in the next generation, mice with the genotype of the ES cells are born (Capecchi, 1989; Rossant and Joyner, 1989).        (2) When murine ES cells are injected subcutaneously into syngeneic mice, teratoma tumors develop. These tumors comprise cells of all three embryonic origins (endoderm, ectoderm and mesoderm) (Wobus et al., 1984).        (3) When murine ES cells are allowed to aggregate in vitro so as to form embryoid bodies (EBs), the cells differentiate in the EBs into various cell types (Robertson, 1987).        
During maturation of murine ES cells in vitro, in addition to morphological changes, a cell may acquire a molecular marker characteristic of a differentiated cell type, such as ζ-globin (a marker of hematopoietic cells) (Wiles and Keller, 1991; Lindenbaum and Grosveld, 1990), neurofilament-68 kd protein (a marker of neuronal cells) (Bain et al., 1995; Levinson-Dushnik and Benvenisty, 1997), and albumin (a marker of hepatic cells) (Levinson-Dushnik and Benvenisty, 1997).
ES cell lines have also been established from primates such as the common marmoset (Thomson. 1996), and the rhesus monkey (Thomson, 1995). However, EB formation by marmoset ES cells is inconsistent and asynchronous, and differentiation of the rhesus ES cells is disorganized and vesicular structures do not form (Thomson, 1998a).
Human ES cell lines have been established derived from human embryos produced by in vitro fertilization (Thomson, 1998b). The embryos were cultured to the blastocyst stage and inner cell masses comprising ES cells were isolated and cultured. These human ES cells are only known to be capable of differentiating when in teratomas (Thomson, 1998b). When cultured in vitro, the human ES cells have normal karotypes, express telomerase activity, and proliferate. However, the inability to produce EBs from non-human primate ES cells led to the belief that EBs could also not be formed from human ES cells (Thomson, 1998a).